This is an application for renewal of the Integrative Program in Complex Biological Systems (ipCBS), a graduate training program providing a specialization for students that are members of the Biophysics and Bioinformatics group. The ipCBS is a comprehensive interdisciplinary program specifically designed around the engineering of complex biological systems (?synthetic biology?). At a fundamental level, this program seeks to solve the sociological and linguistic problems associated with training scientists and engineers to be simultaneously conversant in the multiple languages of biology, mathematics, physics, and engineering. A key feature of the ipCBS is the fact that UCSF is medical campus, so that our students can exploit opportunities to explore and engineer biological complexity in the context of health and disease. Over the past grant period, the ipCBS has continued to develop and evolve the curriculum, especially in the area of hands-on project based, experiential learning. As a result, a purpose-built Graduate Teaching Laboratory was constructed as a direct outcome of this training program, and projects-based courses conducted in the spirit of Cold Spring Harbor / Woods Hole, have become a keystone of the graduate first year experience. The key points of the ipCBS are as follows: ? Long term objective: To provide critical training necessary to lead innovation in a synthetic and systems biology research environment driven by team-based interdisciplinary approaches to biomedical science and human health and dominated by large-scale and high complexity data characteristic of precision medicine. ? Approach: The ipCBS holds four core principles as the basis for graduate training. 1) Focus on the ?design principles? of biological organization, from the molecular to the cellular level. 2) Focus on the challenge of engineering synthetic circuitry within complex systems from an interdisciplinary team-based perspective. 3) Focus on breaking down the language/sociology barrier. 4) Focus on mentoring.